Abstract
Intestinal microbiota facilitates food breakdown for energy metabolism and influences the immune response, maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression or if it could modulate the risk of acquiring the HIV infection. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha (p = 0.040) and beta diversity (p = 0.006) compared to HC, but no differences were found compared to HIV+. A lower Treg percentage was observed in HESN (1.77%) than HC (2.98%) and HIV+ (4.02%), with enrichment of the genus Butyrivibrio (p = 0.029) being characteristic of this profile. Moreover, we found that Megasphaera (p = 0.017) and Victivallis (p = 0.0029) also are enriched in the microbiota composition in HESN compared to HC and HIV+ subjects. Interestingly, an increase in Succinivibrio and Prevotella, and a reduction in Bacteroides genus, which is typical of HIV-infected individuals, were observed in both HESN and HIV+, compared to HC. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.
Highlights
Resistance to Human Immunodeficiency Virus 1 (HIV-1) in uninfected individuals who have repeated unprotected sexual exposure to the virus, known as HIV-1-exposed seronegative (HESN), provides a unique opportunity to elucidate mechanisms of natural protection to infection
Recent studies demonstrated that gut microbiota, composed of over 100 trillion bacteria residing at the gastrointestinal tract (GIT), facilitates food breakdown for energy metabolism and contributes to the immune system’s development and function, maintaining mucosal homeostasis [5,6]
We identified common genera of Firmicutes such as Faecalibacterium and Roseburia genus with similar abundance in the fecal microbiota in all groups analyzed (Fig 1A), microbiota in HIV-exposed seronegative individuals (HESN) was different compared to healthy control (HC)
Summary
Resistance to Human Immunodeficiency Virus 1 (HIV-1) in uninfected individuals who have repeated unprotected sexual exposure to the virus, known as HIV-1-exposed seronegative (HESN), provides a unique opportunity to elucidate mechanisms of natural protection to infection. In the HIV context, most studies, including those performed in Latin America, have found that HIV infection is associated with intestinal dysbiosis and changes in diversity, with increased numbers of Enterobacteriaceae and Enterococcaceae pathobionts, as well as by an enrichment of the Prevotella genus [9,10,11,12] This altered microbial profile in HIV+ patients is associated with i) a metabolic alteration of the microbiota and processes related to oxidative stress [13], and with ii) increased levels of activation markers, and reduced levels of IL-10 and IL-1R, which in turn correlate with an increase of activated CD8+ T cells [9,14,15], possibly facilitating infection in HIV-exposed individuals [16]. The presence and abundance of beneficial bacteria within the intestinal microbiota could modulate the development and response of the immune system, decrease activation levels, and promote integrity and function of the intestinal mucosa, protecting against infections such as those caused by enteric pathogens and sexually transmitted viruses as HIV-1 [17,18]
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